Clinical Box 11 Why Doesnt Your Stomach Digest Itself

Tight regulation of the body's pH around 7.4 is a hallmark of homeostasis, the maintenance of a stable internal environment. This is important since biomolecules including catalytic proteins (enzymes) have evolved to function best near a neutral pH, say between pH 7 and 8. For example, higher or lower pHs result in abnormal protonation or deprotonation of protein R groups, which often leads to marked changes in the protein's normal function with the result that strong acids and bases are often considered to be cell toxins.

Consequently, it is striking that parietal cells, located in the stomach wall of humans and other animals, secrete vast quantities of H+ in response to consumption of food. The role of acid secretion by parietal cells is to hydrolyt-ically destroy ingested microorganisms and to denature (unfold) and help hydrolyze (i.e., digest) proteins. In this process, parietal cells create an extracellular pH adjacent to the interior of the stomach wall that is in the vicinity of pH 1, with a resultant pH of about pH 2 to 3 when the secreted acid is mixed into the chyme, or homogenized contents, of the stomach. Exposure of most body tissues to such high acid conditions would result in severe acid burns. This raises the question: How does a gastric mucosa cell then protect itself from the gastric acidity? The answer lies in the fact that there are millions of goblet cells in the gastric mucosa, or stomach lining, that secrete a viscous, aqueous solution of mucus, which also contains HCO3 ions. The mucus with its acid neutralizing HCO3~ buffer forms a thick gel layer that covers the surface of the gastric mucosa and prevents the epithelial cells from contacting the acid chyme.

The weakening of these mucosal defense mechanisms results in ulcerations and eventually gastric ulcer disease. A variety of factors including excessive alcohol and tobacco consumption, stress, and nonsteroidal anti-inflammatory drugs such as aspirin can lead to erosion in the lining of the stomach. Additionally, there is also a positive correlation between Helicobacter pylori (H. pylori) bacterial infection and the incidence of gastric and ulcers of the small intestine. H. pylori produces large quantities of the enzyme urease, which hydrolyzes urea to produce ammonia. The ammonia neutralizes the gastric acid in the bacteria's immediate environment thus protecting the bacteria from the toxic effects of its normally toxic acid environment. It is remarkable how some cells find a way to survive even in the deadliest environment.

The importance of pH to the life processes becomes even clearer when we consider the fact that there are a series of weak electrolyte chemical systems in organisms whose principal role is to maintain a viable pH. The main players in this complex system of acid/base buffers are phosphoric acid and carbonic acid, which help maintain a relatively constant internal chemical state, different from the equilibrium state, and which is compatible with life. This life-compatible, internal state is known as homeostasis and applies to all conditions such as pH, osmolarity, temperature, energy supply, and so on. Intracellular and extracellular pH homeostasis is maintained by a complex interplay of the two sets of weak acid dissociation reactions shown in Eqs. (1.14) and (1.15).

H3PO4 L H2PO4_1 + H+ L HPO42 + 2H+ L PO43 + 3H+ (1.14)

For aqueous systems, we generally understand a chemical system to be a most chemically effective acid buffer when there are nearly equal amounts of H+ donors and H+ acceptors available, and when the tendency for H+ to dissociate from the donor species or associate with the acceptor species is equivalent. Chemically these best buffering conditions can be related to the equilibrium constant for the buffering reaction. Phosphoric acid can dissociate 3 H+ each having a different affinity (or equilibrium constant) for the parent molecule so that they each dissociate at a different H+ concentration. Optimal buffering usually occurs at pH values that are numerically related to the equilibrium constant as shown in Eq. (1.16).

pH(max buffer capacity) = pKa where Ka is the equilibrium constant (1.16)

Phosphoric acid dissociates 3 H+, and the three equilibrium constants or pKas for each dissociation are close to 2, 7, and 12, respectively, for the first, second, and third dissociation reactions shown in Eq. (1.14). Since the homeostatic pH is closest to 7.0, it should be clear that in biological systems the bolded reaction step in Eq. (1.14), which dissociates the second of the three H+, is the biologically significant buffer reaction and that H2PO4 and HPO4 ' J are the biologically important H donor and H+ acceptor, respectively.

The situation with the carbonic acid buffer reaction [Eq. (1.15)] is complicated by the fact that this buffer system involves gaseous CO2, which is in abundant supply in the atmosphere and is also a main intracellu-lar product of energy metabolism. Both of these sources of CO2 impact the distribution of the components of the carbonic acid buffer system.

When the partial pressure of CO2 is taken into account in physiologically relevant pH calculations, it is found that under normal atmospheric CO2 partial pressure the carbonic acid/bicarbonate system is a potent contributor to the regulation of human pH homeostasis slightly above pH 7.0.

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  • jaakko
    Why doesnt the stomach digest itself?
    8 years ago

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